The leukemias are a heterogeneous group of neoplasm arising from the malignant transformation of hematopoietic (blood forming) cells. Leukemic cells proliferate primarily in bone marrow and lymphoid tissues where they interfere with normal hematopoiesis and immunity. Ultimately, they emigrate into the peripheral blood and infiltrate other tissues.
Leukemias are classified according to the cell types primarily involved (myloid and lymphoid) and as acute or chronic based upon the natural history of the disease. Acute leukemias, including acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML), have a rapid clinical course and often result in death within a matter of months without effective treatment. In contrast, chronic leukemias have a more prolonged natural history. Chronic leukemias include chronic lymphocytic leukemia (CCL), chronic myelogenous leukemia (CML) and hairy cell leukemia.
It is of great significance to develop new and effective drugs for the treatment of leukemia. The present invention provides an anti-HLA-DR antibodies and the method of use thereof for treating leukemia, lymphoma or solid tumor.
U.S. Pat. No. 6,416,958 discloses anti-human major histocompatibility complex (MHC) class II, HLA-DR-specific antibodies, which can induce apoptosis of HLA-DR positive cells. However, the '958 patent does not disclose the anti-HLA-DR antibodies that bind to and induce apoptosis of solid tumor cells in the present invention.
U.S. Pat. No. 6,129,914 discloses 1D10 antibodies that specifically bind to malignant B-cells. However, the '914 patent does not disclose the antibody of the present invention, which is a pan anti-HLA-DR, binding to CESS (myelomonocytic leukemia, American Type Culture Collection (ATCC)), Daudi (Burkitts lymphoma, ATCC), KG-1 (acute myelocytic leukemia, ATCC), Raji (Burkitt's lymphoma, ATCC), Ramos (Burkitt's lymphoma, ATCC), RL (non-Hodgkin's lymphoma, ATCC), THP-1 (acute myclocytic leukemia, ATCC), OVCAR-5 (ovarian cancer, ATCC), C32 (melanoma, ATCC), and HT-144 (ATCC).
The present invention provides anti-HLA-DR antibodies. Such antibodies induce apoptosis of various types of lymphoma cells, leukemia cells, preferably AML cells, or Burkitts lymphoma cells, and some solid tumor cells, preferably ovarian or melanoma cancer cells. The anti-HLA-DR antibodies can be used for the treatment of leukemia, lymphoma or solid tumor.